N,O-Dimethyl-4-(2-naphthyl)piperidine-3-carboxylate
# N,O-Dimethyl-4-(2-naphthyl)piperidine-3-carboxylate

N,O-Dimethyl-4β-(2-naphthyl)piperidine-3β-carboxylate (DMNPC) is a piperidine based stimulant drug which is synthesised from arecoline. It is similar to nocaine in chemical structure, and has two and a half times more activity than cocaine as a dopamine reuptake inhibitor. However it is also a potent serotonin reuptake inhibitor, with similar affinity to fluoxetine.

Ki Affinity of Piperidine Based MAT Inhibitors :

| ∗∗ | X | N | 5HT | DA | NE |
| - | - | - | - | - | - |
| SS | p-Vinyl | Me | 138 | 131 | 175 |
| SS | p-Ethyl | Me | 255 | >1.7K | >1.1K |
| SS | p-Allyl | Me | 309 | 964 | >1K |
| SS | p-Ethynyl | Me | 175 | 187 | 364 |
| SS | p-Phenyl | Me | 62 | 173 | 203 |
| SS | β-Naphthyl | Me | 7.6 | 21 | 34 |
| 3R,4S | β-Naphthyl | Me | 42 | 947 | 241 |
| RR | β-Naphthyl | Me | 192 | 87 | 27 |
| 3S,4R | β-Naphthyl | Me | 12 | 271 | 38 |
| 3S,4R | β-Naphthyl | $H_2Cl$ | 3.5 | 90 | 30 |
| SS/RR | α-Naphthyl | Me | 101 | 304 | 281 |

The stereochemistry of DMNPC dramatically affects it's binding affinity with the SS enantiomer having the highest overall activity. The 3R,4S enantiomer demonstrates the highest selectivity for 5-HTT.

In animal studies, DMNPC exhibits similar potency as fluoxetine but with greater activity for DAT and NET. N-Demethylation of DMNPC has shown to produce a 3-fold increase in potency for 5-HTT.

## Synthesis

A racemic mixture of DMNPC can be synthesized from freebase arecoline in a grignard reaction with 2-naphthylmagnesium bromide. Further reactions and separation methods can be used to produce enantiomerically pure products.

A substantially simpler method that ablates the carbomethoxy ester substituent has been demonstrated by D. Koch in Ex2: U.S. Patent 6,303,627

